Device for use in normalizing readings on a testing machine

ABSTRACT

An optic module verification device for normalizing between X photon counters, including a verification tray with X verification wells and a modular photon emitter in each verification well. Each photon emitter includes a spring, a Beta source disk, a scintillator disk adjacent the Beta source disk, and a neutral density filter over the scintillator disk, all of which are encapsulated in a cylindrical chamber with the filter adjacent an opening on one end of the chamber and the spring biasing the Beta source disk and the scintillator disk toward the opening. The device is periodically used for normalization, and may be updated when emitted photons fall below a desired level by replacing the scintillator disk and then determining a new normalized reference values for each photon emitter.

CROSS REFERENCE TO RELATED APPLICATION(S)

This application is a division of U.S. application Ser. No. 11/637,314,filed Dec. 12, 2006.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not applicable.

REFERENCE TO A MICROFICHE APPENDIX

Not applicable.

TECHNICAL FIELD

The present invention relates to normalizing readings on testingmachines, and more particular to normalizing photon count readings ontesting machines having more than one photon counter.

BACKGROUND OF THE INVENTION AND TECHNICAL PROBLEMS POSED BY THE PRIORART

Testing of biological samples is often carried out using, for example,wet chemistry, in conjunction with automatic testing machines. In somesuch tests, samples are dispensed in reaction trays having a pluralityof wells for handling a plurality of samples, with the analysis of thedifferent samples often involving counting photons emitted from thesamples. There is no known single photon counting standard, however,and, therefore, it is only possible to obtain relative relationshipsbetween single photon sources and photon detectors (photon counters).

Further, there is an intrinsic variability among photomultiplier tubesused to count photons, which variability requires a normalization methodto obtain similar count values among different photon counters, such asare typically encountered in testing machines (a plurality of photoncounters facilitates higher volume testing). In such cases, for examplewith the ABBOTT PRISM™ System available from Abbott Laboratories, Inc.of 100 Abbott Park Road, Abbott Park, Ill. 60064, the testing machinemay have a plurality of different tracks for different types of tests,with each track having two photon counters, which are used inconjunction with trays having a plurality of rows of wells, with eachrow having two wells (e.g., two columns of wells in eight rows). In use,a tray is advanced through the testing machine row by row, with onephoton counter counting photons emitted from each well of one column ofwells and the second photon counter counting photons emitted from eachwell of the other (adjacent) column of wells.

Given the intrinsic variability and extremely sensitive nature of photoncounters, however, it is essentially impossible to expect that each ofthe photon counters will be identical, or will obtain identical resultseven under identical conditions (which can never be achieved in anyevent). Therefore, it has been necessary to normalize the readingsobtained by different photon counters, that is, to determine a factor ofdifference between the photon counters, which may be used to obtaincomparable results among a plurality of photon counters. For example, ina simplified example, if a known source is read, and one photon counteris found to return readings that are 10% higher than the known source,and the other photon counter is found to return readings that match whatwould be expected from the known source, readings taken during testingby the former photon counter would be reduced to take into account the10% overcount, thereby giving test results that are therefore morereliable. Of course, accurate test results are particularly critical inmany such biological testing situations, because incorrect results arenot merely testing failures, but may also result in a misdiagnosis of anindividual's condition and subsequent improper treatment of a patient.

In order to determine normalization values among photon counters of atesting machine, optic module verification tools (OMVT) have heretoforebeen used. Such devices are essentially duplicates of reaction trays,including at least one well in each column (i.e., associated with eachphoton counter) having a known photon emitter.

The well of a tray 10 including such a prior art photon emitter in oneof the wells of the tray is illustrated in FIG. 1. Specifically, thephoton emitter 20 is disposed beneath a tray well 22, and includes anoptic standard 26 contained within a capsule 28, both of which rest on acap 30. Suitably secured over the optic standard 26 is a filter glass34, and a foam support 36 is provided at the bottom of the tray 22 toassist in locating the filter glass 34 at the desired position adjacentthe bottom of the tray well 22. The optic standard 26 is carbon-14 (C₁₄)mixed with a suitable epoxy resin as a soup or slurry, which is thencast in the desired plug shape.

For normalization, the photon emission of each photon emitter is firstmeasured according to a standard. For example, normalization trays havebeen measured at a central location where such standardized measurementscan take place, with each photon emitter assigned the measured photoncount. Such normalization trays have then been distributed for use withtesting machines, with one normalization tray provided at eachgeographic location where a testing machine is found.

At each testing machine, the normalization tray is run through themachine one or more times in order to obtain a photon count by eachphoton counter from the photon emitter associated therewith. The photonscounted at the test machine by each photon counter are then beencompared to the assigned measured photon count as previously determinedfor each photon emitter, with those values used to normalize the resultsobtained by the different photon counters, when photons emitted fromtest specimens are subsequently counted.

Unfortunately, while the photon emitter such as described above might bethought to be subject to little decay, because it is based on C₁₄ havinga long half-life (5568 years), experience has shown that the photonsemitted by such emitters in fact may decay relatively quickly, so thatthe quantity of emitted photons may fall below a desired minimum levelin as short a period of time as a few months. In that case, a new opticmodule verification device (normalization tray) can be obtained from thecentral location (or the old one must be essentially completelyremanufactured with a new photon emitter) with normalization valuesobtained against the standard. Alternatively, the device can continue tobe used after being re-measured according to the standard, but withphoton emissions that are below the preferred minimum level for reliablenormalization of the test machine. Neither option is preferred for bothcost and operational reasons.

The present invention is directed toward overcoming one or more of theproblems set forth above.

SUMMARY OF THE INVENTION

In one aspect of the present invention, an optic module verificationdevice is provided for use for periodic normalization of a testingmachine used to test samples in wells of reaction trays, where thetesting machine includes X photon counters, which each count photonsemitted from different tray wells, where X is an integer greater than 1.The verification device includes a verification tray defining at least Xverification wells and a photon emitter in each verification well. Theverification wells are located so as to each be associated with adifferent one of the photon counters when used in the testing machine.Each photon emitter includes a C₁₄ source, a scintillator adjacent theC₁₄ source, and a filter over the scintillator, wherein each photonemitter has a determined initial base value for emitted photons, andeach photon emitter is positioned in its verification well to emitphotons through the filter to the associated photon counter when used inthe testing machine.

In one embodiment of this aspect of the present invention, the filter isa neutral density glass filter.

In another embodiment of this aspect of the present invention, thescintillator is a plastic element with opposite generally flat surfaces.In a further embodiment, one surface of the scintillator is abraded,e.g., roughened, to minimize internal reflectivity.

In still another embodiment of this aspect of the present invention, theverification device includes an open bottom tray in each of theverification wells, and the photon emitters are positioned beneath thebottom of the tray with the filter adjacent the opening in the bottom ofthe tray. In a further embodiment, a capsule is removably securable to acap to define a space therebetween for enclosing the photon emitter, thecapsule including a shoulder surrounding an opening against which thefilter is secured, and a spring is positioned between the cap and theC₁₄ source to bias the C₁₄ source and the scintillator against thefilter. In still a further embodiment, the capsule shoulder is alignedwith the opening in the bottom of the tray.

In yet another embodiment of this aspect of the present invention,additional wells in the verification device are closed to preventemission of photons, with the additional wells each being positioned soas to be associated with one of the photon counters.

In another embodiment of this aspect of the present invention, thetesting machine is adapted to count photons of a selected wavelength oflight based on designed wet chemistry for a test specimen, and thescintillator mimics the selected wavelength of light.

In still another embodiment of this aspect of the present invention, theC₁₄ source comprises a steel disk having a surface adjacent thescintillator, the surface coated with C₁₄ having about five (5)micro-curies of activity.

In yet another embodiment of this aspect of the present invention, aMylar coating overlies the C₁₄ coating on the surface of the steel disk.

In another aspect of the present invention, a modular photon emitter isprovided, the emitter including a spring, a disk including a Betasource, a plastic scintillator disk adjacent the Beta source, a neutraldensity filter over the scintillator disk, and a bottom cap and acapsule securable together to define a cylindrical chamber with anopening at one end of the capsule. The spring, the disk including a Betasource, the plastic scintillator disk, and the filter are encapsulatedin the cylindrical chamber with the filter adjacent the aforementionedopening at one end of the capsule and the spring biasing the diskincluding a Beta source and the plastic scintillator disk toward theopening.

In one embodiment of this aspect of the present invention, the surfaceof the scintillator disk adjacent the Beta source disk is roughened.

In another embodiment of this aspect of the present invention, the Betasource is C₁₄.

In still another embodiment of this aspect of the present invention, thecapsule includes an annular face surrounding the opening, and the filteris secured against the annular face.

In yet another embodiment of this aspect of the present invention, thebottom cap and the capsule include mating threads for releasablysecuring the bottom cap and the capsule together.

In still another aspect of the present invention, a method is providedfor periodically normalizing two photon counters of a testing machineused to test samples in wells of reaction trays by counting photonsemitted from the wells of the reaction trays. The method includes thestep of (a) initially providing a verification device having two photonemitters, each photon emitter including a C₁₄ source, a scintillatoradjacent the C₁₄ source, and a filter over the scintillator. Then, instep (b) normalized reference values for each photon emitter aredetermined, in step (c) photons emitted from the photon emitters of theverification device are counted on the testing machine, wherein one ofthe photon counters counts the photons emitted from one of the photonemitters and the other photon counter counts the photons emitted fromthe other photon emitter, in step (d) normalization values for thephoton counters are determined based on the normalized reference valuesand the photons emitted from the photon emitters counted by the photoncounters, in step (e) samples are tested in wells of the reaction trayby counting photons using the two photon counters, and in step (f) thevalues of photons counted from the samples are normalized using thenormalization values. Then, in step (g), steps (e) and (f) are repeatedto test a plurality of reaction trays having wells with samples therein,and in step (h), steps (c) and (d) are periodically repeated. When thecounted photons in step (c) fall below a predetermined value, theverification device is updated by replacing the scintillator of eachphoton emitter, and repeating steps (b) through (h).

In one embodiment of this aspect of the present invention, thescintillators are chosen so that the photon emitters each have aninitial reference value for emitted photons as determined in step (b)within a selected range, with the predetermined value being the lowerend of the selected range.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross sectional view of a well of a normalization trayaccording to the prior art;

FIG. 2 is an exploded view of a photon emitter according to the presentinvention;

FIG. 3 is an exploded view of a normalization tray according to thepresent invention;

FIG. 4 is a cross-sectional view of two wells of a normalization trayaccording to the present invention, with one well including a photonemitter;

FIG. 5 is a plan view of the normalization tray according to the presentinvention;

FIG. 6 is a perspective view illustrating use of the normalization trayaccording to the present invention with a testing machine having twophoton counters;

FIG. 7 is a graph illustrating the decay of photon emissions during theuseful life of a normalization tray according to the prior art; and

FIG. 8 is a graph illustrating the decay of photon emissions during theuseful life of a normalization tray according to the present invention.

DETAILED DESCRIPTION OF THE INVENTION

A normalization tray 100 with photon emitters 102 for use in normalizingreadings on a testing machine or instrument 104 (see FIG. 6) isillustrated in FIGS. 2-5.

The tray 100 includes a base 110 beneath a reaction tray 112 defining aplurality of wells 114, specifically sixteen wells 114 in two columns ofwells having eight rows (see FIG. 3). It should be appreciated that notall of the wells are used with this normalization tray 100, but thatsuch a configuration is advantageously used to match the configurationof trays used in testing so that the normalization tray 100 can beconveniently handled in the testing machine 104. Thus, screw plugs 120can be advantageously secured in those wells 114 that are not actuallyused for normalization (e.g., by securing those plugs in threadedinserts 122 in the tray base 110 as shown in FIG. 4).

A photon emitter 102 according to the present invention is illustratedin FIGS. 2 and 4. The photon emitter 102 includes a stainless steelknurled bottom cap 130 with a suitable spring member 132 (e.g., a wavespring such as illustrated) disposed therein. Supported above the springmember 132 is a C₁₄ source 140, a plastic scintillator disk 146, and asuitable filter glass 150.

The C₁₄ source 140 can advantageously be a steel disk with a C₁₄ platingon the top surface of the disk and a Mylar coating thereon, withsufficient C₁₄ applied to provide about 5 micro-curies of activity.

The scintillator disk 146 absorbs energy emitted by the C₁₄ source 140and, in response, fluoresces photons at a characteristic wavelength. Thematerial of the plastic scintillator disk 146 can thus be selected so asto generate photons at the wavelength to be detected by the testingmachine 104. For example, if the testing machine 104 operates to countphotons in a blue wavelength (e.g., about 420 nanometers) to determinewet chemistry test results for biological samples, a plasticscintillator disk 146 that will emit photons at about 420 nanometers(such as a polyvinyl toluene disk) can advantageously be chosen forinclusion in the photon emitter 102. For example, an Eljen-212 plasticscintillator disk (having a polyvinyltoluene polymer base, and availablefrom Eljen Technology, 300 Crane Street, Sweetwater, Tex. 79556) havinga half inch diameter and 0.020 inch thickness can be used.

Further, it has been found that abrading, e.g., roughening or sanding,at least one flat surface of the scintillator disk 146 (so as to nothave the smoother surface generally produced by molding of such disks)will advantageously minimize internal reflectivity of the plasticscintillator disk 146. For example, sanding of the material of theplastic scintillator disk can be advantageously performed using arandom-orbital sander and 400 grit sandpaper, with the sanding (wet ordry) performed to yield a uniform scoring/dullness of the cast sheet ofscintillation material. The operation is done to yield a level ofscoring/dullness involving only the briefest exposure to the sander,with the sanding removing less than 5% of the original thickness of thecast sheet of scintillation material. Glass-bead blasting is anothermethod that has also been found to acceptably mar the plasticscintillator disk 146. Preferably, only the side of the plasticscintillator disk 146 that faces the Beta source (C₁₄ source 140) issanded, with the other side of the plastic scintillator disk 146 beingleft alone.

The filter glass 150 serves to knock back some of the light, and therebyhelps the photon counters (photodiscriminators) better count singlephoton events. For example, a Schott NG-5 neutral grey glass densityfilter can be advantageously used (e.g., a filter having a half inchdiameter and thickness of about 0.079 inch).

A cylindrical stainless steel capsule 160 is configured so as toencapsulate the spring 132, the C₁₄ source 140, the plastic scintillatordisk 146, and the filter glass 150. As best shown in FIG. 2, the capsule160 includes an outer threaded portion 162 so that it can be secured tothe bottom cap 130 by screwing into an inner thread 164 of the bottomcap 130. Further, the upper end of the capsule 160 is tapered so as togenerally match the underside of the tapered well 114 of the reactiontray 112, and the upper end of the capsule 160 further includes adownwardly facing annular surface 168 adapted to be engaged against theupper face of the filter glass 150.

The filter glass 150 can be suitably secured to the capsule 160, bymeans of gluing, by means of a low bloom “super glue” (e.g.,cyanoacrylate glue that does not evaporate out onto the surroundingsurfaces). A relief groove 170 around the capsule's annular surface 168can be advantageously provided for excess glue from that attachment,helping to also ensure that glue does not disadvantageously leak ontothe top of the filter glass 150, through which photons are intended topass.

It should be appreciated, therefore, that the photon emitters 102 willbe reliably configured with the plastic scintillator disk 146 and theC₁₄ source 140 pressed up against the underside of the filter glass 150by the spring 132.

Foam member(s) 180 or other suitable spring-like member(s) can also beadvantageously provided beneath the photon emitter(s) 102 near thebottom of the tray base 110 to ensure that the photon emitter(s) 102 arepositioned precisely as desired, with the filter glass 150 against thebottom of the well 114 defining portion of the reaction tray 112.

As illustrated in FIG. 5, the tray 100 can include a row with two wells114A, 114B with photon emitters 102A, 102B. Adjacent wells 114C, 114Dcan be provided with black pieces of foam material 184 to block theopenings at the bottom of the wells 114C, 114D to provide wells where nophotons will be present (and thereby provide a check when normalizingthe photon counters).

FIG. 6 illustrates how to use the tray 100 of the present invention tonormalize the photon counters of a testing machine or analyzer 104, thatis, as would occur when testing samples (in which test results can bedetermined by counting the photons generated by wet chemistry on, e.g.,biological samples in different wells of a similar tray, with the wetchemistry of the sample generating light via chemical luminescence,wherein the quantity of light emitted is proportional to the chemicalreactivity). The tray 100 is moved through a track 190 of the analyzer104 so as to index the tray wells 114 beneath photodiscriminators orphoton counters 200A, 200B of the analyzer 104. Photon counts arerecorded for at least wells 114A, 114B, and preferably also wells 114C,114D (to verify that essentially no photons are counted at wells 114C,114D). (A suitable shroud surrounding the wells 114 and photon counters200A, 200B can be provided to prevent environmental photons fromaffecting the count; however, that shroud has been omitted from thefigures for the sake of simplification.) In this manner (as discussedbelow and essentially as previously accomplished), the readingsdetermined by the photon counters 200A and 200B can be normalized sothat readings taken during actual tests of samples can be relied upon asaccurate.

Specifically, the tray 100 according to the present invention, oncemanufactured, is first tested by a reference device to determine anormalized verification value for each photon emitter 102A, 102B, andthose verification values are recorded on the tray 100 for each photonemitter 102A, 102B. For example, one of the photon emitters 102A may bedetermined to emit 12,000 photons in a given time frame whereas theother photon emitter 102B may emit only 11,500 photons in that timeframe.

The tray 100 is then sent to a facility for use in connection with thatfacility's testing machine 104, such as a PRISM® testing machineavailable from Abbott Laboratories, Inc. To use, the tray 100 isperiodically run through the testing machine 104, with the recordedverification values of each photon emitter 102A, 102B checked againstthe readings taken by that machine's photon counters 200A, 200B. Duringsuch periodic testing (e.g., once a month or so), the tray 100 is runthrough the testing machine 104, with readings taken of a plurality ofphoton counts (e.g., ten counts) for each photon emitter 102A, 102B.Those readings can be evaluated for consistency (e.g., if the standarddeviation divided by the mean of the readings for a photon emitter 102Aor 102B is greater than 0.1, a problem with the photon counter 200A or200B used to count photons from the emitter 102A or 102B is indicated).

During such use of the tray 100 for normalizing readings in the photoncounters 200A, 200B, it has been found that over time there will be somedecay in the quantity of photons emitted, notwithstanding the longhalf-life of C₁₄. However, for the normalization process, it ispreferred that the photon counts not vary by more than about 10% of theverification values determined for the photon emitters 102A, 102B duringmanufacture.

However, as illustrated in FIG. 7 for the prior art photon emitter 20illustrated in FIG. 1, a tray 10 having an emitter with an initialphoton count of 12,000 has been found to decay to the point of failure,with unacceptably low photon emissions relative to the initialverification values that it can essentially be considered to fail inless than 200 days. At that point, the tray 10 has heretofore beenreturned to the manufacturing facility (e.g., in Dallas, Tex. for thePRISM® testing machine, available from Abbott Laboratories) so that newverification values can be determined, although those values are at amuch lower value than preferred (e.g., less than 10,000 photons in agiven time frame), and will thereafter decay even further. While thetray 10 has then been used thereafter for a while, eventually, thephoton count of the refurbished tray 10 will have fallen so low that itcan no longer be used. At that point (e.g., about a year in total), thetray 10 is no longer suitable for use and a new tray must bemanufactured and shipped to the testing facility to maintain the testingmachine 104.

By contrast, as illustrated in FIG. 8, the photon emitters 102 of thepresent invention have been found to decay much more slowly, such thatunacceptably low photon emissions are not first encountered for nearly1½ years (versus less than 200 days with the prior art). At that point,the tray 100 can be shipped back to the manufacturing facility, and thetray can be advantageously refurbished by merely replacing the plasticscintillator disks 146 in the photon emitters 102. In this case, thephoton counts of the refurbished photon emitters 102 may actually turnout to be higher than in the original tray 100, and thus not only canthe tray 100 be used nearly three times as long (about three yearsversus one year with the prior art tray 10), but after being refurbishedthe photon counts will be in the desirable range.

It should thus be appreciated that the normalization tray 100 and photonemitters 102 according to the present invention are modular andportable. They are also customizable for different light spectra bychanging the configurations and dimensions of the component parts.Moreover, the radioactive source, the plastic scintillator disk, theneutral density filter, and/or the spacing of components can variouslybe changed to provide portable stable normalization sources for a widevariety of instrument reader assemblies, photomultiplier tubes, andother photon counting devices. Further, the components of the presentinvention can be easily manufactured with reliable repeatability.

Still other aspects, objects, and advantages of the present inventioncan be obtained from a study of the specification, the drawings, and theappended claims. It should be understood, however, that the presentinvention could be used in alternate forms where less than all of theobjects and advantages of the present invention and preferred embodimentas described above would be obtained.

1. A modular photon emitter, comprising: a spring; a disk including aBeta source; a plastic scintillator disk adjacent said Beta source; aneutral density filter over said scintillator disk; and a bottom cap anda capsule securable together to define a cylindrical chamber with anopening in said capsule on one end; wherein said spring, Beta sourcedisk, plastic scintillator disk, and filter are encapsulated in saidcylindrical chamber with said filter adjacent said opening on one end ofsaid capsule and said spring biasing said Beta source disk and saidscintillator disk toward said opening.
 2. The photon emitter of claim 1,wherein the surface of said scintillator disk adjacent said Beta sourcedisk is roughened.
 3. The photon emitter of claim 1, wherein said Betasource is C₁₄.
 4. The photon emitter of claim 1, wherein said capsuleincludes an annular face surrounding said opening, and said filter issecured against said face.